Both cats and humans with interstitial cystitis (IC) have exacerbation of clinical signs during stressful periods. Based on previous studies, it is hypothesized that IC cats have a downregulation of their alpha-2 adrenoceptors (alpha2-AR), probably mediated by an increase in norepinephrine (NE). Stress can increase NE release and downregulate alpha2-AR, suppressing their ability to block painful input from the bladder sensory neurons. Autoradiography will be utilized to evaluate alpha2-AR in the bladder trigone and urethra as well as the locus coeruleus in both healthy and affected cats. Twenty four hour urine NE and cerebral spinal fluid will also be analyzed in both populations. Guanfacine, an alpha2-AR agonist, has been shown to decrease plasma norepinephrine. It will be used to assess inhibition of sympathetic outflow on functional sensitivity and anatomic density of alpha2-AR. Urethral and bladder strips from IC cats and healthy cats will be obtained to determine the effect of guanfacine on receptor function in vitro. These studies may prove beneficial in determining the appropriate therapy for clinical signs of IC in humans.